Apparatus and methods for treating tissue

ABSTRACT

Apparatus and methods are provided for thermally and/or mechanically treating tissue, such as valvular structures, to reconfigure or shrink the tissue in a controlled manner. The apparatus comprises a catheter in communication with an end effector which induces a temperature rise in an annulus of tissue surrounding the leaflets of a valve or in the chordae tendineae sufficient to cause shrinkage, thereby causing the valves to close more tightly. Mechanical clips can also be implanted over the valve either alone or after the thermal treatment. The clips are delivered by a catheter and may be configured to traverse directly over the valve itself or to lie partially over the periphery of the valve to prevent obstruction of the valve channel. The clips can be coated with drugs or a radiopaque coating. The catheter can also incorporate sensors or energy delivery devices, e.g., transducers, on its distal end.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.09/898,726 filed Jul. 3, 2001, which is a continuation-in-part of U.S.patent application Ser. No. 09/602,436 filed Jun. 23, 2000, which inturn claims benefit from U.S. Provisional Patent Application Ser. No.60/141,077 filed Jun. 25, 1999, each being incorporated herein byreference in its entirety.

FIELD OF THE INVENTION

The present invention relates to treatment of tissue. More particularly,the present invention provides methods and apparatus for treatingvalvular disease with a catheter inserted into a patient's cardiacchambers, the catheter having an end effector for modifying cardiacstructures, including valve leaflets and support structure.

BACKGROUND OF THE INVENTION

Degenerative valvular disease is the most common cause of valvularregurgitation in human beings. Regurgitation is typically characterizedby an expanded valve annulus or by lengthened chordae tendineae. Ineither case, an increase in the geometry of a valve or its supportingstructure causes the valve to become less effective, as it no longerfully closes when required.

Loose chordae tendineae may result, for example, from ischemic heartdisease affecting the papillary muscles. The papillary muscles attach tothe chordae tendineae and keep the leaflets of a valve shut. Some formsof ischemic cardiac disease cause the papillary muscles to lose theirmuscle tone, resulting in a loosening of the chordae tendineae. Thisloosening, in turn, allows the leaflets of the affected valve toprolapse, causing regurgitation.

It therefore would be desirable to provide methods and apparatus fortreatment of tissue that modify the geometry and operation of a heartvalve.

It would also be desirable to provide methods and apparatus that areconfigured to thermally treat chordae tendineae, the annulus of a valve,or valve leaflets.

It would also be desirable to further provide methods and apparatus thatare configured to mechanically modify the geometry and operation of aheart valve and annulus of a valve either alone or in addition tothermal treatment.

SUMMARY OF THE INVENTION

In view of the foregoing, it is an object of the present invention toprovide methods and apparatus for the treatment of tissue that modifythe geometry and operation of a heart valve.

It is another object of the present invention to provide methods andapparatus that are configured to thermally treat chordae tendineae, theannulus of a valve, or valve leaflets.

It is another object of the present invention to further provide methodsand apparatus that are configured to mechanically modify the geometryand operation of a heart valve and annulus of a valve either alone or inaddition to thermal treatment.

These and other objects of the present invention are accomplished byproviding apparatus and methods for thermally or mechanically treatingtissue, such as valvular structures, to reconfigure or shrink the tissuein a controlled manner, thereby improving or restoring tissue function.Embodiments of the present invention advantageously may be employed tomodify flow regulation characteristics of a cardiac valve or itscomponent parts, as well as to modify flow regulation in other lumens ofthe body, including, for example, the urinary sphincter, digestivesystem valves, leg vein valves, etc., where thermal shrinkage ormechanical reconfiguration of tissue may provide therapeutic benefit.

In a first family of embodiments of the present invention, apparatus isprovided having an end effector that induces a temperature rise in anannulus of tissue surrounding the leaflets of a valve sufficient tocause shrinkage of the tissue, thereby reducing a diameter of theannulus and causing the valves to close more tightly. In a second familyof embodiments, apparatus is provided having an end effector thatselectively induces a temperature rise in the chordae tendineaesufficient to cause a controlled degree of shortening of the chordaetendineae, thereby enabling the valve leaflets to be properly aligned.In yet a third family of embodiments, apparatus is provided having anend effector comprising a mechanical reconfigurer configured to attachto a longitudinal member, such as the chordae tendineae. Thereconfigurer forces the longitudinal member into a tortuous path and, asa result, reduces the member's effective overall or straight length.

Any of these embodiments may employ one or more expanding members thatserve to stabilize the end effector in contact with the tissue orstructure to be treated. In addition, where it is desired to preservethe interior surface of a lumen or structure, the instrument may includemeans for flushing the surface of the tissue with cooled saline. Whereit is desired to achieve a predetermined degree of heating at a depthwithin a tissue or structure, the end effector may comprise a laserhaving a wavelength selected to penetrate tissue to the desired depth,or the end effector may comprise a plurality of electrically conductiveneedles energized by an RF power source, as is known in theelectrosurgical arts. The end effector may alternatively comprise anacoustic heating element, such as an ultrasonic transducer.

In another aspect of the present invention, mechanical clips may beprovided preferably made from shape memory alloys or superelasticalloys, e.g., Nickel-Titanium alloy (nitinol). Such clips may bedelivered to the valve and annulus of tissue surrounding the valve in avariety of ways, e.g., intravascularly, endoscopically, orlaparoscopically, either after the thermal treatment described above, orwithout the thermal treatment. During delivery by, e.g., a catheter, theclips may be compressed into a smaller configuration to facilitatetransport. Upon exiting the catheter, the clips preferably expand to asecond configuration for attachment to the valve tissue. The clips maybe attached to the annulus of tissue surrounding the valve upon beingurged out of the catheter distal end; they may be attached to opposingsides of the valve and preferably have a compressive spring force todraw or cinch the sides of the valve towards one another. The clips maybe configured to traverse directly over the valve itself, but they arepreferably configured to lie partially over the periphery of the valveto prevent obstruction of the valve channel. A central region of theclips may be formed in a variety of geometric shapes, e.g.,semi-circles, arcs, half-ellipses, triangles, rectangles, and loops.Aside from clips, expandable meshes and grids may also be used to drawor cinch the valve edges together.

Moreover, the clips may be coated with therapeutic drugs, which may betime-released, or they may also be coated at least partially with aradiopaque coating to aid in visualization during implantation.

Delivery catheters which may be used to deliver the clips may alsoincorporate sensors or energy delivery devices, e.g., transducers, onthe distal ends. For example, they may be configured as a sensor tomeasure properties, e.g., ultrasound, Doppler, electrode, pressuresensor or transducer, etc., of the tissue prior to catheter withdrawal.Such sensors may also be used to measure properties such as flow rates,pressure, etc. for measurement pretreatment and post-treatment.Alternatively, they may also be used as a transducer to deliver energy,e.g., RF, electrical, heat, etc., to the affected tissue or thesurrounding area by, e.g., either as a separate device or directlythrough the clip itself.

Methods of using apparatus according to the present invention are alsoprovided.

BRIEF DESCRIPTION OF THE DRAWINGS

The above and other objects and advantages of the present invention willbe apparent upon consideration of the following detailed description,taken in conjunction with the accompanying drawings, in which likereference numerals refer to like parts throughout, and in which:

FIG. 1 is a side-sectional view of a human heart showing majorstructures of the heart, including those pertaining to valvulardegeneration;

FIG. 2 is a side view of apparatus of a first family of embodimentsconstructed in accordance with the present invention;

FIGS. 3A-3C are, respectively, a side view of an end effector for usewith the apparatus of FIG. 2 and a sectional view through its catheteralong sectional view line A-A, a side view of an alternative endeffector and a sectional view of its catheter along view line B-B, and aside view of a still further alternative end effector;

FIG. 4 is a sectional view through the human heart, depicting a methodof using the apparatus of FIG. 2 to shrink tissue in an annulussurrounding the leaflets of a regurgitating valve;

FIGS. 5A and 5B are schematic views of alternative embodiments of theapparatus of FIG. 2;

FIGS. 6A-6D are views of a still further alternative embodiment of theapparatus of FIG. 2 having barbs, and illustrating a method of use;

FIGS. 7A-7C are schematic views showing, respectively, an alternativeembodiment of the end effector of FIG. 6 having electrically insulatedbarbs, a method of using the end effector to thermally treat tissue, anda temperature profile within the tissue during treatment;

FIGS. 8A and 8B are side views of another alternative embodiment of theapparatus of FIG. 6 having multipolar, individual electrodes;

FIG. 9 is a side view of an alternative embodiment of the apparatus ofFIG. 8 having individual ultrasonic transducers;

FIG. 10 is a side-sectional view of another alternative embodiment ofthe apparatus of FIG. 8 having individual laser fibers;

FIG. 11 is a side-sectional view of an alternative embodiment of theapparatus of FIGS. 8-10 having individual barb members that may comprisemultipolar electrodes, ultrasonic transducers, or laser fibers;

FIG. 12 is a sectional view through the human heart, illustrating analternative method of introducing apparatus of the first family ofembodiments to a treatment site;

FIGS. 13A and 13B are views of an alternative embodiment of theapparatus of FIG. 2 shown, respectively, in schematic side view and inuse shrinking an annulus of tissue;

FIGS. 14A and 14B are, respectively, a side view of an alternativeembodiment of the apparatus of FIG. 2, and a method of using theembodiment via the introduction technique of FIG. 12;

FIGS. 15A and 15B are isometric views of an alternative end effector foruse with the apparatus of FIG. 14;

FIG. 16 is a top view of apparatus of a second family of embodimentsconstructed in accordance with the present invention;

FIG. 17A-17C are views of end effectors for use with the apparatus ofFIG. 16;

FIG. 18 is a sectional view of the human heart, illustrating a method ofusing the apparatus of FIG. 16 to selectively induce a temperature risein the chordae tendineae sufficient to cause a controlled degree ofshortening of the tendineae;

FIGS. 19A-19C show a section of chordae tendineae and illustrate amethod of shrinking the tendineae in a zig-zag fashion using the endeffector of FIG. 17C with the apparatus of FIG. 16;

FIGS. 20A-20C show, respectively, a side view of an intact tendineae, aside view of the tendineae after treatment by a shrinkage technique, anda cross section through the tendineae along sectional view line C-C ofFIG. 20A after treatment by an alternative shrinkage technique;

FIGS. 21A and 21B are side views of apparatus of a third family ofembodiments, constructed in accordance with the present invention, shownin a collapsed delivery configuration and in an expanded deployedconfiguration;

FIGS. 22A and 22B are schematic views depicting a method of using theapparatus of FIG. 21 to mechanically shorten an effective length ofchordae tendineae; and

FIG. 23 is a side view, partially in section, illustrating a method andapparatus for non-invasive coagulation and shrinkage of scar tissue inthe heart, or shrinkage of the valve structures of the heart.

FIG. 24A is an isometric view of a variation on a valve resizing deviceas an expandable grid with anchoring ends.

FIG. 24B is a top view of another variation on the valve resizing deviceas an expandable mesh.

FIGS. 25A and 25B are side views of exemplary anchors which may be usedwith a valve resizing device.

FIG. 26 is a cross-sectional superior view of a heart section with theatrial chambers removed for clarity with the device of FIG. 24Aimplanted over a valve.

FIGS. 27A and 27B are a top view showing variations on a circumferentialclip.

FIG. 28 is a cross-sectional superior view of a heart section with theatrial chambers removed for clarity with the device of FIG. 27Aimplanted around a valve.

FIGS. 29A and 29B show a side view and an end view, respectively, of avariation on a clip.

FIGS. 30A and 30B show a side view and an end view, respectively, ofanother variation on a clip.

FIGS. 31A-31D show a top, side, end, and isometric view, respectively,of a further variation on the clip.

FIGS. 32A-36B show top and side views of alternative variations on theclip.

FIG. 37 shows a cross-sectional view of a variation on the distalsection of a delivery catheter.

FIG. 38 shows a cross-sectional view of another variation on the distalsection of a delivery catheter where the clip is held in a differentconfiguration.

FIG. 39 shows a cross-sectional view of yet another variation on thedistal section of a delivery catheter.

FIGS. 40A and 40B are top and side views of a variation on a handle forcontrolling the advancement of the clip.

FIGS. 41A and 41B illustrate a cross-sectional view of a heart and apossible method of delivering and implanting a clip over the heartvalve.

FIG. 41C is a cross-sectional view of a heart and a variation on thedelivery catheter having a sensing device or a transducer integrated onthe distal end.

FIGS. 42A-42D are cross-sectional superior views of a heart section withthe atrial chambers removed showing an alternative method of deliveringand implanting clips through the coronary sinus.

FIGS. 43A and 43B are a superior view and a side view of a valve,respectively, showing an alternative clip configuration implanted on thevalve.

DETAILED DESCRIPTION OF THE INVENTION

With reference to FIG. 1, a sectional view through human heart H ispresented. Major structures labeled include the right atrium RA, leftatrium LA, right ventricle RV, left ventricle LV, superior vena cavaSVC, inferior vena cava IVC, and ascending aorta AA. Structures that maybe involved in valvular degeneration and regurgitation are also labeled,including the papillary muscles PM, chordae tendineae CT, valve leafletsL, and annuluses of tissue surrounding the leaflets A, as well as thetricuspid valve TV, the bicuspid or mitral valve MV, and the aorticvalve AV. The pulmonary valve PV is not seen in the cross section ofFIG. 1, but may also experience valvular degeneration. As discussedpreviously, degenerative valvular disease often leads to valvularregurgitation, which is typically characterized by an expanded valveannulus A or by lengthened chordae tendineae CT. Loose chordae tendineaemay result from ischemic heart disease affecting the papillary musclesPM, which attach to the chordae tendineae and act to regulate flowthrough leaflets L.

The present invention therefore provides apparatus and methods forshrinking or reconfiguring tissue, such as annulus A or chordaetendineae CT. The present invention also encompasses optionally alteringa shape of the valve through mechanical attachments. The mechanicalattachments, as discussed in detail below, may be done either after theshrinking or reconfiguring of the tissue, or it may be done as astand-alone procedure. Embodiments of the present inventionadvantageously may be employed to modify flow regulation characteristicsof a cardiac valve or its component parts, as well as to modify flowregulation in other lumens of the body, including, for example, theurinary sphincter, digestive system valves, leg vein valves, etc., wherethermal shrinkage or mechanical reconfiguration of tissue may providetherapeutic benefit.

FIGS. 2-15 illustrate apparatus of a first family of embodiments of thepresent invention. The first family of embodiments have an end effectorthat induces a temperature rise in an annulus of tissue surrounding theleaflets of a valve sufficient to cause shrinkage of the tissue, therebyreducing a diameter of the annulus and causing the valve to close moretightly.

Referring to FIG. 2, apparatus 30 comprises catheter 32 having endeffector 34 in a distal region of the catheter. End effector 34 may becollapsible within and extendable beyond the distal end of catheter 30to permit percutaneous delivery to a treatment site. End effector 34 hasan annular shape to facilitate treatment of an annulus of tissue, aswell as stabilization against the walls of a treatment site.

With reference to FIGS. 3A-3C, alternative embodiments of end effector34 and catheter 32 are described. In FIG. 3A, end effector 34 comprisesexpandable balloon 40. Balloon 40 comprises bipolar electrodes 42 a and42 b that may be attached to a radiofrequency (“RF”) voltage or currentsource (not shown). Balloon 40 further comprises lumen 44 to facilitateunimpeded blood flow or fluid transport therethrough, and temperaturesensors 46 to monitor shrinkage of tissue caused by current flow betweenbipolar electrodes 42 a and 42 b. Sensors 46 may comprise, for example,standard thermocouples, or any other temperature sensor known in theart.

The end effector of FIG. 3A is thus capable of achieving controlledluminal shrinkage while allowing blood to pass through the center ofballoon 40. Electrodes 42 a and 42 b are disposed as bands on theperiphery of balloon 40 and may inject an RF electrical current into thewall of a treatment site, such as an annulus or lumen, to shrinkcollagen contained therein. Furthermore, balloon 40 may be inflated witha circulating coolant C, such as water, to cool the surface of balloon40 and thereby minimize thermal damage at the surface of the treatmentsite. Thermally damaged tissue may be thrombogenic and may form thrombuson its surface, leading to potentially lethal complications.

FIG. 3A also provides a cross section through an embodiment of catheter32, along sectional view line A-A, for use in conjunction with theballoon embodiment of end effector 34. Catheter 32 comprises coolantlumens 48 a and 48 b that may circulate coolant C into and out ofballoon 40, respectively. It further comprises wires 49 a-49 c,electrically coupled to electrode 42 a, electrode 42 b, and temperaturesensors 46, respectively.

In FIG. 3B, an alternative embodiment of end effector 34 and catheter 32is presented. Instead of RF energy, the heating element in thisembodiment is a laser source (not shown) coupled to fiber optic cable 50having side firing tip 51. The laser source injects light energy intothe wall of a treatment site via fiber optic cable 50, thereby thermallyshrinking the tissue. The wavelength of the laser may be selected topenetrate tissue to a desired depth. Furthermore, a plurality of fiberoptic cables 50, coupled to the laser source and disposed about thecircumference of balloon 40, may be provided.

Balloon 40 is substantially transparent to the laser energy, and coolantC may again serve to cool the surface of balloon 40, thereby minimizingdamage at the surface of the treatment site. The circulating stream ofcoolant C maintains the temperature of surface tissue layers at asufficiently low level to prevent thermal damage, and thus, to preventformation of thrombus. Temperature sensor 46 optionally may also beprovided.

As seen in FIG. 3C, end effector 34 may alternatively comprise wrappedsheet 52 incorporating one or more electrodes on its surface. Sheet 52may be advanced to a treatment site in a collapsed deliveryconfiguration within a lumen of catheter 32, and may then be unfurled toan expanded deployed configuration wherein it contacts the interior wallof the treatment site and may be energized to shrink tissue.

Referring now to FIG. 4, a method of using apparatus 30 to thermallyshrink an annulus of tissue is described. End effector 34 is placed inintimate contact with the inner wall of a blood vessel or other bodylumen. In the valvular regurgitation treatment technique of FIG. 4, endeffector 34 is percutaneously delivered just proximal of aortic valve AVwithin ascending aorta AA at annulus of tissue A supporting leaflets L,using well-known techniques. Aortic valve AV suffers from valvulardegeneration, leading to regurgitation. End effector 34 delivers energyto annulus A sufficient to heat and shrink the annulus, thus enhancingfunction of the degenerative valve.

Collagen within annulus A shrinks and reduces a diameter of the annulus.Leaflets L are approximated towards one another, as seen in dashedprofile in FIG. 4, and valvular regurgitation is reduced or eliminated.In addition to valvular regurgitation, the technique is expected toeffectively treat aortic insufficiency.

End effector 34 stabilizes apparatus 30 against the wall of a bodypassageway. Once stabilized, a source of energy may be applied to thewall to thermally shrink the tissue contained in the wall. In additionto the application of FIG. 4, treatment may be provided, for example, tothe annulus of mitral valve MV, to the urinary sphincter for treatmentof incontinence, to digestive system valves for treatment of acidreflux, to leg vein valves, and to any other annulus of tissue wheretreatment is deemed beneficial.

With reference to FIGS. 5A and 5B, alternative embodiments of theapparatus of FIG. 2 are described. In FIG. 5A, apparatus 60 comprisescatheter 62 having a lumen, in which end effector 64 is advanceablydisposed. End effector 64 comprises monopolar electrode 66, which isfabricated in an arc from a shape memory alloy, such as spring steel ornitinol, to approximate the shape of an annulus of tissue at a treatmentsite within a patient. Electrode 66 may be retracted within the lumen ofcatheter 62 to facilitate transluminal, percutaneous delivery to thetreatment site. Once in position, electrode 66 may be advanced out of adistal region of catheter 62. The electrode resumes its arc shape andapproximates the wall of the treatment site.

Monopolar electrode 66 is electrically coupled to RF source 68, which ispositioned outside of the patient. RF source 68 is, in turn, coupled toreference electrode 69. When RF source 68 is activated, current flowsbetween monopolar electrode 66 and reference electrode 69, which may,for example, be attached to the exterior of the patient in the region ofthe treatment site. RF current flows into the wall of the treatmentsite, thereby effecting annular tissue shrinkage, as describedpreviously.

In FIG. 5B, a bipolar embodiment is provided. Apparatus 70 comprisescatheter 72 and end effector 74. End effector 74 comprises a pluralityof atraumatic tipped legs 76 that are electrically coupled by aplurality of current carrying wires 78 to an RF source (not shown). Theplurality of legs contact the wall of a treatment site and injectcurrent into the wall. The current flows between the tips of the legs.Alternatively, the plurality of legs may comprise a monopolar electrodecoupled by a single wire to the RF source, and current may flow betweenthe plurality of legs and a reference electrode, as in FIG. 5A.

Referring to FIGS. 6A-6D, another alternative embodiment of theapparatus of FIG. 2 is described. FIG. 6A shows apparatus 80 inside-sectional view in a retracted delivery configuration. Apparatus 80comprises catheter 82 and end effector 84. Catheter 82 further comprisescentral bore 86, a plurality of side bores 88, and optional temperaturesensors 90. End effector 84 may, for example, be fabricated from nitinolor spring steel, and comprises conductive shaft 92 having a plurality ofradially extending electrodes 94 with optional barbs 96. Conductiveshaft 92 is electrically coupled to RF source 98, which is electricallycoupled to reference electrode 99. Conductive shaft 92 is disposedwithin central bore 86, while electrodes 94 are disposed within sidebores 88.

End effector 84 is advanceable with respect to catheter 82. Whenadvanced distally, apparatus 80 assumes the expanded deployedconfiguration of FIG. 6B, wherein electrodes 94 extend through sidebores 88 beyond the surface of catheter 82. Apparatus 80 is alsoconfigured such that its distal region may approximate the shape of anannulus of tissue, as described hereinbelow with respect to FIG. 6D, andis thus suited for both linear and circular subsurface tissuecoagulation and shrinkage.

FIGS. 6C and 6D provide a method of using apparatus 80 to treat annulusof tissue A surrounding a heart valve. Apparatus 80 is percutaneouslyadvanced to the surface of a heart valve in the delivery configurationof FIG. 6C. Once positioned at annulus A, the distal region of apparatus80 approximates the shape of the annulus, as seen in FIG. 6D. This maybe accomplished, for example, with a steering mechanism comprising twopurchase points or a pre-shaped tip that is retracted within a straightguiding catheter to allow insertion into the vascular system, asdescribed in U.S. Pat. No. 5,275,162, which is incorporated herein byreference. Once inserted, the pre-shaped tip is advanced out of theguide catheter and recovers its preformed shape.

With apparatus 80 approximating annulus A, end effector 84 is distallyadvanced with respect to catheter 82, thereby selectively advancingelectrodes 94 into the annulus. RF source 98 then provides RF current,which flows between electrodes 94 and reference electrode 99. Theannulus of tissue shrinks; bringing valve leaflets into proper positionand minimizing or eliminating regurgitation through the valve.

Catheter 82 insulates conductive shaft 92 from annulus A, therebyprotecting surface tissue and only allowing coagulation at depth intreatment zones surrounding electrodes 94. To further ensure thatcoagulation only occurs at depth, a coolant, such as saline, may beintroduced through central bore 86 and side bores 88 of catheter 82 tothe surface of annulus A, thereby cooling and flushing the area whereelectrodes 94 penetrate the tissue. It is expected that such liquidinfusion will keep the surface of the annulus clean and will preventthrombus formation in response to thermal damage.

Referring now to FIG. 7A-7C, an alternative embodiment of end effector84 of FIG. 6 is described. The end effector of FIG. 7 is equivalent tothe end effector of FIG. 6 except that it is coated with electricallyinsulating layer I. Insulation layer I covers the entire exterior of endeffector 84, except at the distal ends of the plurality of electrodes94. The layer is preferably sufficiently thin to allow insertion ofelectrodes 94 into tissue T without impediment. The exposed distal endsof the electrodes are configured to deliver energy into subsurfacetissue at treatment zones Z. The zones may be ideally modeled as spheresof subsurface tissue. Tissue shrinks within treatment zones Z withoutdamaging surface tissue, as seen in FIG. 7B.

The size of treatment zones Z may be controlled to ensure that tissueremodeling only occurs at depth. Assuming a temperature T₁, at whichtissue damage is negligible, the magnitude of current passed throughtissue T may be selected (based on the material properties of the tissueand the depth of insertion of electrodes 94 within the tissue) such thatthe temperature decays from a temperature T₀ at a position D₀ at thesurface of an electrode 94 to the benign temperature T₁ at a distance D₁from the surface of the electrode. The distance D₁ may be optimized suchthat it is below the surface of tissue T. An illustrative temperatureprofile across a treatment zone Z is provided in FIG. 7C.

With reference to FIGS. 8A and 8B, another alternative embodiment of theapparatus of FIG. 6 is described. Apparatus 100 comprises catheter 102and end effector 104. End effector 104 further comprises a plurality ofindividual, multipolar electrodes 106, which are electrically coupled toan RF or other current source (not shown) by a plurality of currentcarrying wires 108. As with the embodiments of FIGS. 6 and 7, apparatus100 is configured such that end effector 104 may approximate an annulus,as seen in FIG. 8B.

Referring to FIGS. 9-11, alternative embodiments of the apparatus ofFIG. 8 are described. In FIG. 9, apparatus 110 comprises catheter 112and end effector 114. End effector 114 comprises a plurality of acousticheating elements 116. Acoustic elements 116 may, for example, compriseultrasonic transducers. The acoustic energy may further be focused byappropriate means, for example, by lenses, such that a tissue damagethreshold sufficient to cause shrinkage is only attained at a specifieddepth within treatment site tissue, thereby mitigating surface tissuedamage and thrombus formation. Acoustic elements 116 are connected toappropriate controls (not shown). Apparatus 110, and any other apparatusdescribed herein, may optionally comprise temperature sensors 118.

In FIG. 10, apparatus 120 comprises catheter 122 and end effector 124.Catheter 122 comprises a plurality of central bores 126 and a pluralityof side bores 128, as well as a plurality of optional temperaturesensors 130. End effector 124 comprises a plurality of side-firing fiberoptic laser fibers 132 disposed within central bores 126 of catheter122. The fibers are aligned such that they may deliver energy throughside bores 128 to heat and induce shrinkage in target tissue. Fibers 132are coupled to a laser source (not shown), as discussed with respect toFIG. 3B. Suitable wavelengths for the laser source preferably range fromvisible (488-514 nm) to infrared (0.9-10.6 microns), wherein eachwavelength has an ability to heat tissue to a predetermined depth. As anexample, a preferred laser source comprises a continuous wave laserhaving a 2.1 micron wavelength, which will shrink and heat tissue to adepth of 1-2 mm.

In FIG. 11, apparatus 140 comprises catheter 142 and end effector 144.Catheter 132 comprises central bores 146 and side bores 148. Catheter132 further comprises temperature sensors 150 that are configured topenetrate superficial tissue layers to measure temperature at depth.Temperature sensors 150 may be retractable and extendable to facilitatepercutaneous delivery of apparatus 140. End effector 144 comprisesfibers 152 disposed within central bores 146. Fibers 152 are retractablewithin and extendable beyond side bores 148. Fibers 152 are preferablysharpened to facilitate tissue penetration and energy delivery tosubsurface tissue, thereby inducing shrinkage of the tissue.

Fibers 152 may comprise any of a number of energy delivery elements. Forexample, fibers 152 may comprise a plurality of optical fibers coupledto a laser (not shown). The wavelength of the laser may be selected asdescribed hereinabove, while the energy deposited by the fibers may becontrolled responsive to the temperature recorded by sensors 150. Thus,for example, a controller (not shown) may be provided to switch off thelaser once a preset temperature, for example, 45° C.-75° C., isattained, thereby ensuring that a sufficiently high temperature isachieved to cause tissue shrinkage without inadvertently damagingsurrounding tissues.

Fibers 152 may alternatively comprise a plurality of multipolarelectrodes. Each electrode may be capable of injecting RF energy intotissue independently. Alternatively, current may be passed between apair of adjacent or non-adjacent electrodes to heat intervening tissue.

Referring now to FIG. 12, an alternative method of introducing apparatusof the first family of embodiments to a treatment site is described.Apparatus 30 of FIG. 2 is been introduced to the annulus of tissue Asurrounding mitral valve MV via the venous circulatory system. Catheter32 is transluminally inserted via the jugular vein and superior venacava SVC. The distal end of the catheter or a separate instrument thenpenetrates atrial septum AS using a procedure known as septostomy. Oncethe septum is perforated, end effector 34 may be inserted into leftatrium LA and positioned over mitral valve annulus A to effect thethermal treatment described hereinabove. The tricuspid valve in theright ventricle, and the pulmonic valve, may also be treated in the samemanner using a venous approach.

Referring to FIGS. 13A and 13B, a further alternative embodiment of theapparatus of FIG. 2 is described that may be introduced using thetechnique of FIG. 4, the technique of FIG. 12, or by another suitabletechnique. Apparatus 160 comprises catheter 162 and end effector 164.End effector 164 comprises adjustable, heatable loop 166, which isconfigured for dynamic sizing to facilitate positioning next to tissueat a treatment site. The size of loop 166 is adjusted so as to liecontiguous with annulus of tissue A at a treatment site, as seen in FIG.13B. The loop may be collapsible within catheter 162 to facilitatepercutaneous delivery and is electrically coupled to RF source 168,which is electrically coupled to reference electrode 170. Loop 166 maybe fabricated from nitinol, copper, or any other suitably conductive andductile material.

Referring to FIGS. 14A and 14B, a still further alternative embodimentof the apparatus of FIG. 2, and a method of using the embodiment withthe introduction technique of FIG. 12, is described. Apparatus 170comprises catheter 172 and end effector 174. End effector 174 is capableof grabbing and penetrating tissue, as well as delivering RF energy intotissue. End effector 174 comprises jaws 176 a and 176 b, which arespring-biased against one another to a closed position. By pushing aknob on the handpiece (not shown), the jaws may be actuated to an openposition configured to grab tissue at a treatment site. RF energy maythen be deposited in the tissue in a monopolar or bipolar mode. Jaws 176may optionally be coated with electrically insulating layer I everywhereexcept in a distal region, such that tissue is only treated at depth, asdescribed hereinabove. End effector 174 has temperature sensor 178 tocontrol power delivered to the tissue, again as described hereinabove.

With reference to FIG. 14B, a method of using apparatus 170 via aseptostomy introduction technique to treat mitral valve regurgitation isdescribed. In particular, jaws 176 of end effector 174 are actuated toengage individual sections of valve annulus A so as to penetrate intothe collagenous sublayers and to thermally shrink those sublayers. Theprocedure may be repeated at multiple locations around the perimeter ofannulus A until regurgitation is minimized or eliminated.

FIGS. 15A and 15B show an alternative end effector for use withapparatus 170 of FIG. 14. End effector 180 is shown in an open positionand in a closed position, respectively, and comprises jaws 182 a and 182b. End effector 180 is similar to end effector 174, except that jaws 182are configured to engage tissue with a forceps grasping motion whereinbent tips 184 a and 184 b of the jaws are disposed parallel to oneanother and contact one another when closed.

With reference now to FIGS. 16-20, apparatus of a second family ofembodiments of the present invention are described. These embodimentsare provided with an end effector that selectively induces a temperaturerise in the chordae tendineae sufficient to cause a controlled degree ofshortening of the chordae tendineae, thereby enabling valve leaflets tobe properly aligned.

A preferred use for apparatus of the second family is in treatment ofmitral valve regurgitation. Mitral valve regurgitation has many causes,ranging from inherited disorders, such as Marphan's syndrome, toinfections and ischemic disease. These conditions affect themacromechanical condition of the mitral valve and prevent the valve fromclosing completely. The resulting gap in the leaflets of the valvepermit blood to regurgitate from the left ventricular chamber into theleft atrium.

Mechanically, the structural defects characterizing mitral valveregurgitation include: (1) the chordae tendineae are too long due to agiven disease state; (2) papillary muscle ischemia changes the shape ofthe papillary muscle, so that attached chordae tendineae no longer pullthe leaflets of the mitral valve completely shut; (3) the annulus of themitral valve becomes enlarged, resulting in the formation of a gapbetween the leaflets when closed; and (4) there is an inherent weaknessin the leaflets, leaving the leaflets floppy and dysfunctional.

In accordance with the principles of the present invention, atemperature rise is induced in the support structure of the mitral valveto cause shrinkage that modifies the geometry of the valve to restoreproper stopping of blood backflow and thereby regurgitation. Thisprocess is depicted in FIGS. 18-20 using the apparatus of FIGS. 16 and17 to selectively shrink portions of the chordae tendineae, therebybringing leaflets of the mitral valve leaflets into alignment. Apparatusof the second family may also be used in treatment of aortic valveregurgitation, and in treatment of a variety of other ailments that willbe apparent to those of skill in the art.

Referring to FIG. 16, apparatus 200 comprises catheter 202 and endeffector 204. Catheter 204 optionally comprises collapsible andexpandable stabilizer 206, configured to stabilize apparatus 200 in abody lumen. Stabilizer 206 may comprise, for example, struts or aninflatable balloon.

End effector 204 may be collapsible to a delivery configuration withincatheter 202, and may expand to a delivery configuration beyond a distalend of the catheter. End effector 204 is configured to engage, heat, andshrink chordae tendineae. Various sources of energy may be used toimpart heat to the collagenous tissue and thereby shrink it, includingRF energy, focused ultrasound, laser energy, and microwave energy. Inaddition, chemical modifiers, such as aldehydes, may be used. For laserembodiments, a preferred laser is a continuous wave Holmium:Yag laser,with application of visible or infrared laser energy in the wavelengthrange of 400 nanometers to 10.6 micrometers.

With reference to FIGS. 17A-17C, embodiments of end effector 204 aredescribed. In FIG. 17A, the end effector comprises a gripping mechanismthat carries the heating element. Arms 210 a and 210 b are opposing andspring-biased against each other. The arms may be actuated to an openposition using a handpiece (not shown) coupled thereto. Arms 210 a and210 b may alternatively be vertically displaced with respect to oneanother to allow the arms to cross-cross and tightly grasp tissue.Heating elements 212 and temperature sensors 214 are attached to thearms. Heating elements 212 may comprise electrodes, acoustictransducers, side-firing laser fibers, radioactive elements, etc. It maybe desirable to employ a saline flush with heating elements 212 toprevent coagulation of blood caught between arms 210.

FIG. 17B shows an embodiment of end effector 204 with fixed, straightarms 220 a and 220 b. The arms are configured to engage and disengagechordae tendineae simply by being positioned against the tendineae. FIG.17C shows an embodiment of the end effector having arms 230 a and 230 b.Multiple heating elements 212 are disposed on arm 230 a. When heatingelements 212 comprise bipolar electrodes, current flow through thetendineae using the embodiment of FIG. 17C may be achieved primarilyalong a longitudinal axis of the tendineae, as opposed to along a radialaxis of the tendineae, as will be achieved with the embodiment of FIG.17A. These alternative heating techniques are described in greaterdetail hereinbelow with respect to FIGS. 19 and 20.

Referring to FIG. 18, a method of using apparatus of the second familyof embodiments to induce shrinkage of chordae tendineae CT is described.Catheter 202 of apparatus 200 is advanced percutaneously, usingwell-known techniques, through the ascending aorta AA and aortic valveAV into the left ventricle LV, with end effector 204 positioned withinthe catheter in the collapsed delivery configuration. Stabilizer 206 isthen deployed to fix catheter 202 in ascending aorta AA, therebyproviding a stationary leverage point.

End effector 204 is expanded to the deployed configuration distal ofcatheter 202. The end effector is steerable within left ventricle LV tofacilitate engagement of chordae tendineae CT. End effector 204, as wellas any of the other end effectors or catheters described herein, mayoptionally comprise one or more radiopaque features to ensure properpositioning at a treatment site. End effector 204 is capable of movingup and down the chordae tendineae to grab and selectively singe certainsections thereof, as illustrated in dotted profile in FIG. 18, toselectively shorten chordae tendineae CT, thereby treating valvularregurgitation.

When energy is transmitted through tissue utilizing one of theembodiments of this invention, the tissue absorbs the energy and heatsup. It may therefore be advantageous to equip the end effector withtemperature or impedance sensors, as seen in the embodiments of FIG. 17,to output a signal that is used to control the maximum temperatureattained by the tissue and ensure that the collagen or other tissuesintended to be shrunk are heated only to a temperature sufficient forshrinkage, for example, a temperature in the range of 45° C.-75° C., andeven more preferably in the range of 55° C.-65° C. Temperatures outsidethis range may be so hot as to turn the tissue into a gelatinous massand weaken it to the point that it loses structural integrity. A closedloop feedback system advantageously may be employed to control thequantity of energy deposited into the tissue responsive to the output ofthe one or more sensors. In addition, the sensors may permit theclinician to determine the extent to which the cross-section of achordae has been treated, thereby enabling the clinician to heat treatonly a portion of the cross-section.

This technique is illustrated in FIGS. 19 and 20, in which alternatingbands, only a single side, or only a single depth of the chordae isshrunk to leave a “longitudinal intact fiber bundle.” This method may beadvantageous in that, by avoiding heat treatment of the entire crosssection of the chordae, there is less risk of creating mechanicalweakness.

FIGS. 19A-19C depict a method of shrinking a section of chordaetendineae CT in a zig-zag fashion using the embodiment of end effector204 seen in FIG. 17C. In FIG. 19A, the tendineae has an initialeffective or straight length L₁. Arms 230 engage chordae tendineae CT,and heating elements 212 are both disposed on the same side of thetendineae on arm 230 a. The heating elements may comprise bipolarelectrodes, in which case the path of current flow through tendineae CTis illustrated by arrows in FIG. 19A.

Collagen within the tendineae shrinks, and chordae tendineae CT assumesthe configuration seen in FIG. 19B. Treatment zone Z shrinks, and thetendineae assumes a shorter effective length L₂. Treatment may berepeated on the opposite side of the tendineae, as seen in FIG. 19C, sothat the tendineae assumes a zig-zag configuration of still shortereffective length L₃. In this manner, successive bands of treatment zonesZ and intact longitudinal fiber bundles may be established.

An additional pair of bipolar electrodes optionally may be disposed onarm 230 b of the end effector to facilitate treatment in bands onopposite sides of chordae tendineae CT. The depth of shrinkage attainedwith apparatus 200 is a function of the distance between the electrodes,the power, and the duration of RF energy application. If, laser energyis applied, the wavelengths of energy application may be selected toprovide only partial penetration of the thickness of the tissue. Forexample, continuous wave Holmium:YAG laser energy having a wavelength of2.1 microns penetrates a mere fraction of a millimeter and may be asuitable energy source.

FIGS. 20A-20C illustrate additional shrinkage techniques. Intact chordaetendineae CT is seen in FIG. 20A. FIG. 20B demonstrates shrinkage withapparatus 200 only on one side of the chordae, using the techniquedescribed with respect to FIG. 19. FIG. 20C demonstrates shrinkage with,for example the end effector of FIG. 17A or 17B, wherein, for example,bipolar current flows across the tendineae and treats the tendineaeradially to a certain preselected depth. When viewed in cross-sectionalong sectional view line C-C of FIG. 20A, chordae tendineae CT has anintact longitudinal fiber bundle core C surrounded by treatment zone Z.

With reference to FIGS. 21-22, apparatus of a third family ofembodiments of the present invention are described. These embodimentsare provided with an end effector comprising a mechanical reconfigurerconfigured to engage a longitudinal member, such as the chordaetendineae. The reconfigurer forces the longitudinal member into atortuous path and, as a result, reduces the member's effective overallor straight length.

Referring to FIGS. 21A and 21B, apparatus 300 comprises catheter 302 andend effector 304. End effector 304 comprises mechanical reconfigurer306, adapted to mechanically alter the length of a longitudinal member,for example, chordae tendineae. Reconfigurer 306 comprises a preshapedspring fabricated from a shape memory alloy, for example, nitinol,spring steel, or any other suitably elastic and strong material.Reconfigurer 306 is preshaped such that there is no straight paththrough its loops. Overlap between adjacent loops is preferablyminimized. The shape of reconfigurer 306 causes longitudinal members,such as chordae tendineae, passed therethrough to assume a zig-zagconfiguration and thereby be reduced in effective length. Reconfigurer306 is collapsible to a delivery configuration within catheter 302, asseen in FIG. 21A, and is expandable to a deployed configuration, as seenin FIG. 21B. The reconfigurer optionally may be selectively detachablefrom catheter 302.

With reference to FIGS. 22A and 22B, a method of using apparatus 300 tomechanically shorten chordae tendineae CT is described. Apparatus 300 isadvanced to the chordae tendineae, for example, using the techniquedescribed hereinabove with respect to FIG. 18. End effector 304 is thenexpanded from the delivery configuration seen in FIG. 22A to thedeployed configuration of FIG. 22B. Mechanical reconfigurer 306 regainsits preformed shape, and chordae tendineae CT is passed through atortuous path that reduces its effective length, thereby treatingvalvular regurgitation. Reconfigurer 306 may then be detached fromapparatus 300 and permanently implanted in the patient, or thereconfigurer may be left in place for a limited period of time tofacilitate complementary regurgitation treatment techniques.

Other embodiments of the third family in accordance with the presentinvention will be apparent to those of skill in the art in light of thisdisclosure.

Referring now to FIG. 23, apparatus in accordance with the presentinvention is described that may be used as either an embodiment of thefirst family or of the second family. Apparatus and methods are providedfor noninvasively coagulating and shrinking scar tissue around theheart, or valve structures inside the heart, using energy delivered viahigh intensity, focused ultrasound. Apparatus 350 comprises catheter 352and end effector 354. End effector 354 comprises ultrasonic transducer356 and focusing means 358, for example, a lens. Focused ultrasound ispropagated and directed with a high level of accuracy at the chordae CT,the annuluses A of the valves or at a section of bulging wall of theheart, using, for example, echocardiography or MRI for guidance. As withthe previous embodiments, the shrinkage induced by energy deposition isexpected to reduce valvular regurgitation. Apparatus 350 may also beused to reduce ventricular volume and shape, in cases where there isbulging scar tissue on the wall of the left ventricle LV secondary toacute myocardial infarction.

Alternatively, various mechanical valve resizing systems and methods maybe used in conjunction with the apparatus and methods discussed above.Optionally, the various mechanical valve resizing systems and methods,as discussed below, may be used as a stand-alone system. Thesemechanical resizing systems may generally entail the positioning,deployment, and securing of one or more clips to bring the annular edgesof a valve, e.g., a heart valve, or opening together to correct forvalvular regurgitation. This would typically result in the reduction ofthe effective diameter of the valve or opening. The clip is preferablymade of superelastic or shape memory materials, e.g., Nickel-Titaniumalloys, because of the ability of these types of materials to be easilyformed, e.g., by annealing, into desirable geometries. Such materialsare very strong and have the ability to be constrained into a reduceddiameter size for deployment as well as being capable of providing apermanent compressive spring force.

The variations of clip geometries described herein may be manufacturedin several ways. One method involves securing a wire, band, or othercross-sectioned length, preferably made of a superelastic or shapememory material, to a custom forming fixture (not shown). The fixturepreferably has a geometry similar to the valve or opening where thecompleted clip is to be placed and the fixture preferably has a diameterwhich is smaller than the diameter of the valve or opening. The fixturediameter may be determined by the amount of closure by which the valveor opening may need to be closed or approximated to reduce or eliminatevalvular regurgitation. The fixture, with a constrained clip placedthereon, may be subjected to a temperature of about 500° to 700° F.preferably for a period of about 1 to 15 minutes. Additional detailsabout the processing and performance of superelastic and shape memorymaterials may be seen in U.S. Pat. No. 5,171,252 to Friedland, which isincorporated herein by reference in its entirety. The fixture and clipmay then be removed and subjected to rapid cooling, e.g., quenching incold water. The clip may then be removed from the fixture and the endsof the clip may be trimmed to a desired length. The trimmed ends mayalso be formed into a sharpened point by, e.g., grounding, to facilitatepiercing of the tissue.

FIG. 24A shows a variation of a valve resizing device in expandable grid360. Grid 360 is shown as having alternating member 362 formed of acontinuous alternating length while forming several anchoring regions364, which may be radiused. The number of alternating members (andnumber of resultant anchoring regions 364) formed may be determined by avariety of factors, e.g., the geometry of the valve to be resized or theamount of spring compression required. Grid 360 is preferably made of ashape memory alloy, as discussed above. The terminal ends of alternatingmember 362 preferably end in anchoring ends 366. Anchoring ends 366 maydefine a range of angles with the plane formed by alternating member362, e.g., 45°, but is preferably formed perpendicular to the plane.Ends 366 may be formed integrally from alternating member 362, which mayfirst be cut to length, by reducing a diameter of ends 366 to form,e.g., a barbed end or double-barbed end as shown in the figure and inthe detail view. Alternatively, anchoring ends 366 may be formedseparately and attached to the ends of alternating member 362 by, e.g.,adhesives, welding, or scarf joints. The ends 366 are shown in thisexample as a double-barbed anchoring fastener, but generally any type offastening geometry may be used, e.g., single-barbs, semi-circular ortriangular ends, screws, expandable locks, hooks, clips, and tags, orgenerally any type of end geometry that would facilitate tissueinsertion yet resist being pulled or lodged out. Also, sutures andadhesives, as well as the barbs, may be used to fasten grid 360 to thetissue.

Another variation on a grid-type device is shown in FIG. 24B asexpandable mesh 368. In this variation, several individual interwovenmembers 370 may be woven together to form a continuous mesh. Members 370may be either welded together or loosely interwoven to form expandablemesh 368. In either case, the geometries of both expandable grid 360 andmesh 368 are formed to preferably allow a compressive spring force yetallow a relative degree of expansion once situated on the valve oropening.

To maintain grid 360 or mesh 368 over the valve or opening, fastenerslocated around the valve or opening are preferably used for anchoringgrid 360 or mesh 368. Fasteners are preferably made of a biocompatiblematerial with relatively high strength, e.g., stainless steel orNickel-Titanium. Biocompatible adhesives may also be used. A variationof such a fastener is shown in FIG. 25A. Anchor 372 is shown having abarbed distal end 374 for piercing tissue and for preventing anchor 372from being pulled out. Shown with a double-barb, it may also besingle-barbed as well. Stop 376, which is optional, may be locatedproximally of distal end 374 to help prevent anchor 372 from beingpushed too far into the tissue. A protrusion, shown here as eyelet 378,is preferably located at the proximal end of anchor 372 and may extendabove the tissue surface to provide an attachment point. Grid 360 ormesh 368 may be looped through eyelet 378 or they may be held to eyelet378 by sutures or any other conventional fastening methods, e.g.,adhesives.

Another variation on fasteners is shown in FIG. 25B. Here, lockinganchor 380 is shown with distal end 382 having pivoting orbutterfly-type lock 384. Stop 386 is preferably located proximally ofdistal end 382 and protrusion (or eyelet) 388 is preferably located atthe proximal end of locking anchor 380. In use, pivoting lock 384 may beretracted against the shank of anchor 380 while being pushed into thetissue. When anchor 380 is pulled back, pivoting lock 384 may extendoutwardly to help prevent anchor 380 from being pulled out of thetissue.

FIG. 26 shows a cross-sectional superior view of, e.g., human heartsection 390, with the atrial chambers removed for clarity. Heart tissue392 is seen surrounding tricuspid valve 400 and bicuspid or mitral valve402. Sectioned ascending aorta 394 and pulmonary trunk 396 are also seenas well as coronary sinus 398 partially around the periphery of heartsection 390. An example of expandable grid 360 in a deployedconfiguration is shown over tricuspid valve 400. Grid 360 may be placedentirely over valve 400 and anchored into heart tissue 392 by anchors404, which may be of a type shown in FIG. 25A or 25B, at anchoringregions 364. Once grid 360 is in place, it may impart a spring forcewhich may draw the opposing sides of valve 400 towards one another,thereby reducing or eliminating valvular regurgitation.

Another variation on a biasing clip device is shown in FIGS. 27A and27B. FIG. 27A shows circumferential clip 406 having opposing members408. This clip variation, preferably made of a shape memory alloy, e.g.,Nickel-Titanium alloy, may be inserted into the tissue surrounding avalve. This clip may surround the periphery of the valve and provide aninwardly biased spring force provided by opposing members 408 to atleast partially cinch the valve. The variation in FIG. 27A preferablysurrounds about 50% to 75% of the valve circumference. The variation ofclip 410 is shown in FIG. 27B with opposing members 412. Here, the clipmay be made to surround at least about 50% of the valve circumference.FIG. 28 again shows the cross-sectional superior view of heart section390 except with circumferential clip 406 placed in the tissue 392 aroundvalve 400. As shown, opposing members 408 preferably provide theinwardly biased spring force to at least partially cinch valve 400.

A further variation of the clip is shown generally in FIGS. 29A and 29B.A side view of valve clip 414 is shown in FIG. 29A having anchoringmembers 416 on either end of clip 414. FIG. 29B is an end view of valveclip 414. FIGS. 30A and 30B likewise show another variation of valveclip 418 with curved anchoring members 420 on either end of the clip.This variation of valve clip 418 shows the addition of curved centralregion 422 which may be located near or at the center of clip 418.Region 422 may be incorporated to act as a stress-relieving mechanism byallowing clip 418 to bend or pivot to a greater degree about region 422than clip 418 normally would. This may also allow for greateradjustability when placing clip 418 over a valve. FIG. 30B shows an endview of the clip.

Another variation is seen in FIGS. 31A to 31D. FIG. 31A shows a top viewof arcuate valve clip 424. Clip 424 preferably has an arcuate centralmember 426, which is shown as a semicircle having a radius, R. Centralmember 426 may serve to act as a stress-relieving member, as describedabove, and it may also be designed to prevent any blockage of the valveby clip 424 itself. Thus, radius, R, is preferably large enough so thatonce clip 424 is placed over the valve, central member 426 lies over thevalve periphery. FIG. 31B shows a side view of the clip. This view showsanchoring members 430 attached by bridging members 428 on either end tocentral member 426. FIG. 31C shows an end view of the clip where theanchoring members 430 and central member 426 are clearly shown to lie intwo different planes defining an angle, α, therebetween. The angle, α,may vary greatly and may range from about 60° to 120°, but is preferablyabout 90° for this variation. Finally, FIG. 31D shows an isometric viewof clip 424 where the biplanar relationship between anchoring members430 and central member 426 can be seen.

The curved anchoring members above are shown as being curved in asemi-circle such that they face in apposition to one other. But anygeometry may be used, e.g., arcs, half-ellipses, hooks, V-shapes ortriangles, and generally any type of end geometry that would facilitatetissue insertion yet resist being pulled or lodged out.

The shape of the clip itself may range from a wide variety ofgeometries. Such geometries may include circles, semi-circles,rectangles, triangles, or any combinations thereof. FIGS. 32A and 32Bshow a top and side view, respectively, of valve clip 432 a andanchoring members 434 a where the entire clip 432 a preferably curves inan arcuate manner. FIGS. 33A and 33B show a top and side view,respectively, of clip 432 b with anchoring members 434 b where clip 432b is in a triangular shape. FIGS. 34A and 34B show a top and side view,respectively, of clip 432 c with anchoring members 434 c where clip 432c is in a rectangular shape. FIGS. 35A and 35B show a top and side view,respectively, of clip 432 d with anchoring members 434 d where clip 432d is a looped section. Likewise in FIGS. 36A and 36B show a top and sideview, respectively, of clip 432 e with anchoring members 434 e whereclip 432 e has a curved section, which may act as a stress-relievingmember. These various clip geometries are presented as examples and inno way limit the scope of the invention.

Any of the above-described clips or any other clip geometry in thespirit of this invention may be coated with a variety of substances. Forexample, a clip may be coated with a hydrophilic (which may be used,e.g., for surface lubricity), anti-thrombosis agent, therapeutic agent,or any other drug coating to prevent, e.g., thrombosis, or to act as adrug delivery mechanism. Such drug coatings may be applied during theclip manufacture or just prior to deployment. Also, the clips may bemade to become more radiopaque by coating them with, e.g.,Nickel-Titanium alloy, Platinum, Palladium, Gold, Tantalum, or any otherbiocompatible radiopaque substance. Such a coating could be applied,e.g., by sputter coating or ion deposition. Moreover, the coating ispreferably applied in a thin enough layer such that it would not affectthe physical properties of the clip material.

The clip may be delivered and placed over or around the valve using avariety of different methods, e.g., endoscopically, laparoscopically, orthrough other conventional methods such as open-heart surgery. Apreferable method and apparatus is to deliver the clip through thevasculature using a delivery catheter and/or guidewire. FIG. 37 shows avariation of such a catheter in the cross-sectioned view of a distalsection of delivery catheter 436. Catheter body 438, which may comprisean outer layer of catheter section 436, may be comprised of a variety ofmaterials, e.g., polyimide, polymeric polyolefins such as polyethyleneand polypropylene, high density polyethylene (HDPE), etc. and ispreferably lubricious to allow easy traversal of the vasculature.Catheter body 438 preferably has delivery lumen 440 defined throughoutthe length of catheter section 436 and may terminate at the distal tipin delivery port 442. Delivery port 442 may be an open port and it maybe sealable during delivery when catheter section 436 traverses thevasculature. At the distal most end of section 436, distal tip 443 maybe placed with delivery port 442 defined therethrough. Distal tip 443may be metallic, e.g., Nickel-Titanium alloy, Platinum, Palladium, Gold,Tantalum, etc. to provide radiopacity for visualization by, e.g., afluoroscope, CT, or PET, and is preferably rounded to be atraumatic tothe vasculature. Catheter section 436 may alternatively use a radiopaquemarker band (not shown) either alone or in addition to tip 443 tofurther aid in visualization.

Clip 444 may be disposed in lumen 440 within catheter section 436; asseen, clip 444 is preferably in a compressed configuration to fit withinlumen 440 during delivery. The clip 444 may be loaded into cathetersection 436 through delivery port 442, or alternatively, through theproximal end of delivery lumen 440 and advanced towards the distal endof catheter section 436. Reinforced liner 446 may surround the areawhere clip 444 is loaded to allow structural reinforcement to catheterbody 438. Liner 446 may also allow constrainment of clip 444 whileallowing forward movement of the clip 444 during deployment. Liner 446may be made from a thin-walled superelastic or shape memory tube and mayalso have a lubricious coating to reduce the amount of force requiredfor deployment of clip 444. Catheter section 436 may be guided withinthe vasculature via a conventional guidewire (not shown), or it may besteered through the vasculature via steering lumen 452 which may containsteerable components, e.g., wire 453, disposed within to steer cathetersection 436. Wire 453 may be a pull-wire, leaf spring, or othersteering-type device.

Once catheter section 436 has reached the target site, clip 444 may beadvanced through delivery port 442 by plunger 448. Plunger 448 ispreferably attached to a distal end of stylet 450, which may run throughthe full length of catheter body 438 to allow manipulation from theproximal end. Plunger 448 may be advanced towards the distal end ofcatheter section 436 to urge clip 444 out of delivery port 442 bymanipulating the proximal end of stylet 450. Stylet 450 may be advancedmanually like a guidewire, or by attaching it to an advancementmechanism, e.g., a thumb-slide. Stylet 450 may also be passed through ahemostatic valve located within catheter body 438, either at a distal orproximal end, to prevent backflow into lumen 440 during insertion anddelivery through the vasculature. The advancement mechanism, discussedfurther below, may be controlled by an indexed linear movementmechanism, e.g., a screw, ratchet, etc., located on a handle at theproximal end of catheter body 438. Once plunger 448 and stylet 450 isadvanced completely, clip 444 may be urged completely through deliveryport 442, where it may then expand or form its deployed configuration.

FIG. 38 shows catheter section 436 with another compressed variation ofclip 454. Here, clip 454 may be compressed into a “U” or “V” shape fordelivery and deployed in the same manner by plunger 448 and stylet 450through delivery port 442, as discussed above. This variation enablesthe ends of clip 454 to be deployed simultaneously; however, thisvariation may also require a larger delivery port 442 than the variationshown in FIG. 37.

FIG. 39 shows a further variation of the distal end of deploymentcatheter section 456. This variation shows catheter body 458 withdelivery lumen 460 terminating in distal tip 461, much like thevariations shown above. But here, distal tip 461 does not have adelivery port defined through it, rather delivery port 462 is preferablydefined along a distal length of catheter body 458 proximally of distaltip 461. Clip 464 may be any of the variational shapes described abovebut is shown here in a compressed arcuate shape. Clip 464 may be heldwithin catheter section 456 by an external constraining sheath or it maybe held simply by friction fitting clip 464 within delivery port 462.Catheter section may be steered to the desired target site via steeringlumen 468 and once in position, deployment stylet 466 may be urgedtowards the distal end of section 456 in much the same manner asdescribed above. However, stylet 466 is preferably angled at its distaltip to facilitate pushing clip 464 out through delivery port 462.

FIGS. 40A and 40B show a top and side view, respectively, of an exampleof catheter handle 470 which may be used to advance the clip intoposition over a valve or opening. This variation shows handle 470 withdistal end 472, where the catheter is preferably attached, and thelinear advancement mechanism, shown here as thumb-slide 474. Thumb-slide474 may be advanced in advancement slot 476 towards distal end 472 tourge the plunger and stylet. Within handle 470, the advancement ofthumb-slide 474 may be controlled by an indexing mechanism, e.g., ascrew, ratchet, or some type of gear, which may allow the proximal anddistal movement of the thumb-slide 474 through slot 476.

Delivering and placing the clip over the desired tissue, valve, oropening may be accomplished by several different methods. As shown inFIG. 41A, one exemplary method is to introduce deployment catheter 478into the coronary vasculature through, e.g., the jugular vein, and intothe superior vena cava SVC. From there, tricuspid valve TV may betreated or the mitral valve MV may be treated by having catheter 478penetrate the atrial septum AS using a septostomy procedure, asdiscussed above. Once septum AS is perforated, catheter distal end 480may be inserted into the left atrium LA and brought into position overthe mitral valve MV. Catheter distal end 480 may be positioned overmitral valve MV by tracking its position visually through a fluoroscopeor other device by using the radiopaque distal tip (as described above)or via a radiopaque marker band or half-marker band 486. As shown,distal end 480 may be brought into contact against or adjacent to oneside of the annulus of tissue A. The plunger may be advanced (asdescribed above) to then urge a first end of clip 484 out throughdelivery port 482 and into the annulus of tissue A.

Then, as shown in FIG. 41B, distal end 480 may be moved or steered tothe opposite side of the annulus of tissue A after or while the rest ofclip 484 is advanced through delivery port 482. The distal end 480 ispreferably moved to the opposite side of the mitral valve MV at about180°, if possible, from the initial contact point to allow for optimalreduction of the diameter of the valve. Once distal end 480 ispositioned on the opposing side of the valve, the plunger may then befinally advanced so that the remaining second end of clip 484 exitsdelivery port 482 and engages the annulus of tissue A.

The variations described above may incorporate a variety of sensors ortransducers in the delivery catheter to ensure adherence or optimal clipperformance. For instance, as seen in FIG. 41C sensor/transducer 485,e.g., ultrasound, Doppler, electrode, pressure sensor or transducer,etc., may be incorporated into the distal end 480 of the catheter 478.Sensor/transducer 485 may be connected, electrically or otherwise, to asensor monitor 487, which is preferably located outside the body of thepatient and which may be used to record and/or monitor a variety ofsignals generated from sensor/transducer 485. For example, a pressuresensor may be used as sensor/transducer 485. This pressure sensor maythen be used to quantify the treatment effectiveness before catheter 478is withdrawn. In another variation, sensor/transducer 485 (in this case,used as, e.g., a transducer) may be used to deliver energy, e.g., RF,electrical, heat, etc., to enhance the treatment effectiveness, in whichcase monitor 487 may be an electrical or RF power source.

Distal end 480 may also incorporate a grasping and/or releasingmechanism (not shown) to aid in clip release and implantation. Such amechanism may be incorporated on the plunger or stylet, or a separatecatheter may be inserted in conjunction with catheter 478. The graspingand/or releasing mechanism may also be used to temporarily provide anelectrical connection to the clip.

In a further variation for delivering and placing the clip, it may bedeployed through one or more delivery ports located in the side of thecatheter rather than from the distal end. Delivering from the catheterside may be accomplished in much the same manner as described for FIGS.41A-41C above. Alternatively, a catheter may be inserted into thecoronary vasculature, particularly the coronary sinus, via the aorta todeliver the clip. A cross-sectional superior view of mitral valveopening 488 of mitral valve 402 of a patient's heart is seen in FIG.42A. Delivery catheter 490 may be inserted into the coronary sinus 398and positioned adjacent to mitral valve 402 such that delivery ports 492a, 492 b, 492 c are preferably facing in apposition to mitral valve 402.Although three delivery ports are shown in this example, one to anynumber of desired delivery ports may be used. Delivery ports 492 a, 492b, 492 c are preferably located proximally of distal end 494 and theorientation of the ports may be maintained against mitral valve 402 bythe use of an orientation marker 496, which may be, e.g., a half-marker.

Once proper orientation has been determined, a first clip 498 a, whichmay be compressed in catheter 490 may be urged out of delivery port 492a by a plunger and stylet, as described above or twisted out, and pushedthrough a wall of the coronary sinus 398 and through the adjacent hearttissue 392, as shown in FIG. 42B. The clips are preferably made of asuperelastic or shape memory alloy, e.g., Nickel-Titanium alloy (e.g.,nitinol), and are preferably made to expand as it exits catheter 490.Accordingly, clip 498 a may be pushed until the farthest anchoringmember of clip 498 a is in contact with and enters the edge of valve 402farthest from catheter 490. As clip 498 a finally exits delivery port492 a, the anchoring member may exit and then engage the edge of valve402 closest to catheter 490. This procedure may be repeated for severalclips, as seen in FIG. 42C, where first and second clip 498 a, 498 b,respectively, are shown to have already exited and engaged the tissuesurrounding valve 402. FIG. 42D shows the final engagement of third clip498 c having exited delivery port 492 c and engaged the tissuesurrounding valve 402. Once the clips are in place, the compressivespring force of the clips may aid in drawing the opposing sides of valve402 together, thereby drawing or cinching opening 488 close and reducingor eliminating the occurrence of valvular regurgitation through thevalve. The use of three clips is merely exemplary and any number ofdesired or necessary clips may be used.

FIGS. 43A and 43B show the valve of FIGS. 42A-42D and a side view of thevalve, respectively. FIG. 43A shows another example of arcuate clips 500a, 500 b, as described in FIGS. 31A-31D, engaged to mitral valve 402.Arcuate clips 500 a, 500 b are designed such that the curved region ofeach clip is preferably opposite to each other in order to keep opening488 unobstructed. FIG. 43B shows a side view of valve 402 in annulus502. Clips 500 a, 500 b are preferably engaged to the tissue surroundingannulus 502, e.g., to annulus walls 504.

All of the above mentioned methods and apparatus may be delivered notonly intravascularly through catheters, but also through conventionalprocedures such as open-heart surgery. Moreover, all of the abovementioned methods and apparatus may also be used in conjunction withflow-indicating systems, including, for example, color Doppler flowechocardiography, MRI flow imaging systems, or laser Doppler flowmeters. Application of energy from the end effector may be selected suchthat regurgitation stops before the procedure is completed, as verifiedby the flow-indicating system. Alternatively, the procedure may be“overdone” to compensate for expected tissue relapse, withoutcompromising the ultimate outcome of the procedure.

Additionally, all of the foregoing apparatus and methods optionally maybe used in conjunction with ECG gating, thereby ensuring that tissue isat a specified point in the cardiac cycle before energy is depositedinto the tissue. ECG gating is expected to make treatment morereproducible and safer for the patient.

Although preferred illustrative embodiments of the present invention aredescribed above, it will be evident to one skilled in the art thatvarious changes and modifications may be made without departing from theinvention. For instance, variations of the present invention may be usedas permanent or temporary localized tissue retracting devices. Moreover,modified variations may also be used to mechanically expand or dilatetissue, e.g., for use in maintaining open nasal passages. It is intendedin the appended claims to cover all such changes and modifications thatfall within the true spirit and scope of the invention.

1. An apparatus for treating tissue near a valve to modify flow throughthe valve, comprising: a cinching member having a central region and atleast two anchoring regions on opposing ends of the central region, thecinching member being configured for delivery through a catheter to thetissue whereby the cinching member has a first shape during the deliveryand a second shape after the delivery.